WO2013182537A1 - Autoimmune antibodies - Google Patents

Autoimmune antibodies Download PDF

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Publication number
WO2013182537A1
WO2013182537A1 PCT/EP2013/061430 EP2013061430W WO2013182537A1 WO 2013182537 A1 WO2013182537 A1 WO 2013182537A1 EP 2013061430 W EP2013061430 W EP 2013061430W WO 2013182537 A1 WO2013182537 A1 WO 2013182537A1
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WO
WIPO (PCT)
Prior art keywords
seq
autoantibody
egfr
level
human subject
Prior art date
Application number
PCT/EP2013/061430
Other languages
French (fr)
Inventor
Peter Berndt
Barbara Klughammer
Original Assignee
F. Hoffmann-La Roche Ag
Hoffmann-La Roche Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F. Hoffmann-La Roche Ag, Hoffmann-La Roche Inc. filed Critical F. Hoffmann-La Roche Ag
Priority to CA2870015A priority Critical patent/CA2870015A1/en
Priority to JP2015515492A priority patent/JP2015527564A/en
Priority to EP13726532.8A priority patent/EP2858669A1/en
Priority to CN201380027063.XA priority patent/CN104334190A/en
Priority to BR112014028659A priority patent/BR112014028659A2/en
Priority to MX2014014829A priority patent/MX2014014829A/en
Priority to RU2014154144A priority patent/RU2014154144A/en
Priority to KR1020147034217A priority patent/KR20150017344A/en
Publication of WO2013182537A1 publication Critical patent/WO2013182537A1/en
Priority to HK15102727.9A priority patent/HK1202241A1/en

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57423—Specifically defined cancers of lung
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/71—Assays involving receptors, cell surface antigens or cell surface determinants for growth factors; for growth regulators

Definitions

  • the present invention provides methods for identifying patients diagnosed with non-small cell lung cancer who will most benefit from treatment with erlotinib comprising detecting autoantibodies in blood serum of said patients.
  • Tarceva ® is an orally active, potent, inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase (TKI).
  • EGFR epidermal growth factor receptor
  • TKI tyrosine kinase
  • Erlotinib hydrochloride is the active ingredient in Tarceva ® , which is approved as single agent treatment for patients with advanced non- small cell lung cancer (NSCLC) after treatment with chemotherapy, as maintenance treatment for patients not progressing during chemotherapy (1 st line maintenance) or after failure of chemotherapy (2 nd /3 rd line maintenance).
  • Tarceva ® is also approved as first line treatment for patients whose tumor harbors an EGFR activating mutation in the EU. Expression of unusual proteins is common in cancer and viral infection.
  • the mammalian immune system contains a specialized arm that recognizes proteins induced by cellular transformation (neo-antigens) and effectively eliminates cells that express these neo-antigens against which tolerance has not established during development.
  • This arm of the immune system is thought to be effective against viral infections, spontaneous chromosomal and genomic rearrangements caused by errors of the cell division machinery, or carcinogen-induced transforming mutations. While the initial cytotoxic immune response - which is mediated by the recognition of the unusual proteins displayed on MHCI complexes by CD8 + T-cells - is fast and effective, a sustained response against virus infections or aberrant cellular clones requires the co- stimulatory effect of CD4 + T-helper cells which are activated after presentation of extracellular peptides (which can stem from cells lysed in the first phase of the cytotoxic immune response) via MHCII complexes of professional antigen presenting cells.
  • a typical example is the common cancer marker CEA (cancer embryonic antigen). Tumors frequently exhibit faulty protein processing. Prominent examples include proteins that are incorrectly cleaved by cell localization proteases (the presence of autoantibodies against the N-terminal sequence of p53 which is normally cleaved after the protein is targeted to the nucleus is one of the most specific biomarkers of lung cancer) or incorrectly glycosylated by cellular glycosylases (anti-MUCl- antibodies against a form of MUC1 that is incorrectly O-glycosylated is a biomarker for a variety of cancers).
  • cell localization proteases the presence of autoantibodies against the N-terminal sequence of p53 which is normally cleaved after the protein is targeted to the nucleus is one of the most specific biomarkers of lung cancer
  • anti-MUCl- antibodies against a form of MUC1 that is incorrectly O-glycosylated is a biomarker for a variety of cancers
  • WO2011073905 5 relates to tumor markers associated with the progression of a cancer disease from a less progressed stage to a more progressed stage.
  • Unusual (mutated or expressed in abnormal quantities or locations) tumor proteins can invoke an antibody response.
  • Tumor-induced autoantibodies have frequently been observed and their utility as diagnostic markers has been investigated (Albert and Darnell 2004 6 ). While autoantibodies to tumor proteins can be found that have extraordinar specificity, most of them lack the required sensitivity for a diagnostic test. Few reliable epidemiologic and genetic markers that predict erlotinib hydrochloride response are known in the art.
  • EGFR mutations in exon 18-21 were described to be linked with better prognosis as well as with better response to TKI treatment (Paz-Ares, Soulieres et al. 2010 7 ).
  • the only predictive marker currently known is difficult to diagnose as a biopsy of the tumor is needed.
  • At present only about 50% of NSCLC patients are diagnosed with a biopsy (Reck, Hermes et al. 201 I s ).
  • Present invention solves that problem in that it provides a method of diagnosis of non- small cell lung cancer in a human subject.
  • Present invention solves that problem in that it provides a method of diagnosis of non- small cell lung cancer in a human subject by providing antibodies against mutated EGFR sequences.
  • a patient identified by a method as described herein is a patient, in particular a NSCLC patient who will respond to the treatment with erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride.
  • EGFR is normally bound to the cell membrane and not shed to the bloodstream.
  • EGFR is a normal adult protein that is found in large quantities in some adult tissues. Immune tolerance is expected to be established against this protein and many of its variants. Almost all of the sequences belong to the cytoplasmic part of the molecule and are invisible to professional antigen presenting cells. The mutations affect only a small part of the EGFR molecule.
  • a level of said autoantibody representative for a human subject of a healthy population refers to an estimate of the mean level of the autoantibody in serum of a population of patients who do not suffer from NSCLC.
  • a level of said autoantibody representative for a NSCLC patient refers to an estimate of the mean level of the autoantibody in serum of a population of patients who suffer from NSCLC.
  • overall survival refers to the length of time from diagnosis of disease during and after treatment the patient survives.
  • OS all survival
  • PFS progression-free survival
  • a patient's progression- free survival is improved or enhanced if the patient belongs to a subgroup of patients that has a longer length of time during which the disease does not progress as compared to the average or mean progression free survival time of a control group of similarly situated patients.
  • patient refers to any single mammal for which treatment is desired.
  • the "patient” is a human subject. More particularly, the patient is a human subject suffering from cancer, in particular NSCLC.
  • autoantibody is a type of protein manufactured by the immune system of a patient that is directed against one or more of the patient's own proteins.
  • amino acid denotes the group of naturally occurring carboxy a-amino acids comprising alanine (three letter code: ala, one letter code: A), arginine (arg, R), asparagine (asn, N), aspartic acid (asp, D), cysteine (cys, C), glutamine (gin, Q), glutamic acid (glu, E), glycine (gly, G), histidine (his, H), isoleucine (ile, I), leucine (leu, L), lysine (lys, K), methionine (met, M), phenylalanine (phe, F), proline (pro, P), serine (ser, S), threonine (thr, T), tryptophan (trp, W), tyrosine (tyr, Y), and valine (val, V).
  • “therapy” or “treatment” and grammatical variations thereof such as
  • treat refers to clinical intervention in an attempt to alter the natural course of a disease in the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.
  • gene as used herein comprises variants of the gene.
  • variant relates to nucleic acid sequences which are substantially similar to the nucleic acid sequences given by the GenBank accession number.
  • substantially similar is well understood by a person skilled in the art.
  • a gene variant may be an allele which shows nucleotide exchanges compared to the nucleic acid sequence of the most prevalent allele in the human population.
  • a substantially similar nucleic acid sequence has a sequence similarity to the most prevalent allele of at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%.
  • variants is also meant to relate to splice variants.
  • mutation refers to changes in a genomic sequence. These random sequences can be defined as sudden and spontaneous changes in the cell. Mutation can result in several different types of change in sequences; these can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely.
  • sequences can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely.
  • sequences can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely.
  • sequence mutation refers to a change in the genetic structure that is neither inherited nor passed to offspring.
  • recommending a treatment refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to identify the patient as suitably treated or not suitably treated with a therapy.
  • the therapy may comprise a drug.
  • the information or data may be in any form, written, oral or electronic.
  • using the information or data generated includes communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof.
  • communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof.
  • communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional.
  • the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level.
  • the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample.
  • the information or data includes an indication that the patient is suitably treated or not suitably treated with a therapy comprising said drug.
  • the therapy is erlotinib.
  • providing a diagnosis refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to diagnose a disease in the patent.
  • the information or data may be in any form, written, oral or electronic.
  • using the information or data generated includes presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof.
  • presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof.
  • presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional.
  • the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level.
  • the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample.
  • the information or data includes an indication that the patient is diagnosed with said disease. In some embodiments, said disease is non-small cell lung cancer.
  • biopsy material had been collected and the tumor cells have been tested for the presence of the most frequent somatic mutations, i.e. a deletion at exon 19, and a point mutation at exon 21.
  • serum samples had been collected at various time points (pre-dose, day 8, day 22 and progression) from all patients and were assessed for autoantibodies against EGFR.
  • autoantigenic peptide sequences that predict development of rash, or prolonged progression free or overall survival inevitably include a set of sequences that are derived from the EGFR sequence starting at position 737 and extending through 756.
  • These peptides include a number of sequence variants, but inevitably include sequences that have a deletion at position 746-750 or close nearby (Table 2).
  • somatic EGFR mutation in exon 19 in tumor tissue leads to protein variant against that the immune system has not developed tolerance.
  • the somatic mutation occurs only in the tumor, and therefore, if it induces an autoantibody which can be detected in the patient's serum it can be used to draw conclusions about the presence of an exon 19 mutation or exon 21 mutation in the NSCLC tissue, which is well known to predict increased progression free survival and superiority of tyrosine kinase monotherapy over chemotherapy (Hovi and Reck 2011 11 ).
  • the autoantibody can be detected using a standard blood sample from the patient without the need to obtain tumor cells with a biopsy. This is a large advantage over the current practice, as recovery rates of useful tumor samples even in clinical studies do not exceed 50% (Reck, Hermes et al. 2011 12 ).
  • Anti-EGFR autoantibodies can be detected in blood samples of NSCLC patients at higher concentrations than in healthy controls ( Figure 1).
  • peptide sequences have been identified that yield consecutive regions of high immunogenicity with large differences between patient and healthy controls sera. Consecutive sequence stretches were identified, where ratios of individual peptide signals in more than 30% of the cancer patients to maximum value in controls was larger than 8 (Table 1).
  • EGFR peptide sequences selected from Seq. Id. No. 1 - Seq. Id. No. 15 are consecutive sequences with high auto antigenicity in NLSCL patients.
  • EGFR peptide sequences selected from Seq. Id. No. 16 - Seq. Id. No. 517 are useful for predicting the occurrence and grade of adverse events like rash to erlotinib treatment.
  • EGFR peptide sequences selected from Seq. Id. No. 518 - Seq. Id. No. 602 are antigenic sequences influencing, in particular extending, progression free and overall survival of NSCLC patients, in particular mutated EGFR peptide sequences Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559 and Seq. Id. No. 560, as well as EGFR peptide sequences Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521 and Seq. Id. No.561.
  • EGFR peptide sequences selected from Seq. Id. No. 603 - Seq. Id. No. 619 have high predictive potential for prolonged progression free survival in patients with EGFR mutations that develop rash.
  • Antibodies against these peptide sequences most likely influence PFS and OS if they are present in patients. Tests that detect the presence of these antibodies in patient sera could be used to guide treatment and stratify patients into treatment groups.
  • Present onvention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
  • a certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing mutated human EGFR is measured.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id.
  • Seq. Id. No. 42 Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id.
  • Seq. Id. No. 133 Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq.
  • Seq. Id. No. 204 Seq. Id. No. 205
  • Seq. Id. No. 206 Seq. Id. No. 207
  • Seq. Id. No. 208 Seq. Id. No. 209
  • Seq. Id. No. 210 Seq. Id. No. 211
  • Seq. Id. No. 212 Seq. Id. No. 213
  • Seq. Id. No. 214 Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq.
  • Seq. Id. No. 294 Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id.
  • Seq. Id. No. 349 Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq.
  • Seq. Id. No. 405 Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id.
  • Seq. Id. No. 494 Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq.
  • Seq. Id. No. 534 Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq.
  • Seq. Id. No. 590 Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 601, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No.
  • Seq. Id. No. 22 Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id.
  • Seq. Id. No. 104 Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id.
  • Seq. Id. No. 176 Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id.
  • Seq. Id. No. 304 Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No.
  • Seq. Id. No. 359 Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No.
  • Seq. Id. No. 415 Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq.
  • Seq. Id. No. 450 Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No.
  • Seq. Id. No. 504 Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id.
  • Seq. Id. No. 575 Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619..
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No.
  • a certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
  • a certain embodiment of present invention provides erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method as described herein comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
  • a certain embodiment of present invention provides the use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method as described herein.
  • a certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq.
  • Seq. Id. No. 69 Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id.
  • Seq. Id. No. 92 Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id.
  • Seq. Id. No. 104 Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id.
  • Seq. Id. No. 203 Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id.
  • Seq. Id. No. 275 Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No.
  • Seq. Id. No. 292 Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No.
  • Seq. Id. No. 330 Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id.
  • Seq. Id. No. 386 Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq.
  • Seq. Id. No. 475 Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq.
  • Seq. Id. No. 546 Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id.
  • Seq. Id. No. 584 Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
  • a certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
  • a certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer , in particular wherein the level of an autoantibody recognizing human EGFR is measured
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide is selected from the group consisting of Seq. Id.
  • Seq. Id. No. 2 Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13,
  • Seq. Id. No. 14 Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No.
  • Seq. Id. No. 20 Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id.
  • Seq. Id. No. 89 Seq. Id. No. 90
  • Seq. Id. No. 91 Seq. Id. No. 92
  • Seq. Id. No. 93 Seq. Id. No. 94
  • Seq. Id. No. 95 Seq. Id. No. 96
  • Seq. Id. No. 97 Seq. Id. No. 98
  • Seq. Id. No. 99 Seq.
  • Seq. Id. No. I l l Seq. Id. No. 112
  • Seq. Id. No. 113 Seq. Id. No. 114
  • Seq. Id. No. 115 Seq. Id.
  • Seq. Id. No. 190 Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq.
  • Seq. Id. No. 225 Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No.
  • Seq. Id. No. 298 Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 309, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No.
  • Seq. Id. No. 316 Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id.
  • Seq. Id. No. 334 Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq.
  • Seq. Id. No. 370 Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 373, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id.
  • Seq. Id. No. 530 Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq.
  • Seq. Id. No. 600 Seq. Id. No. 601, Seq. Id. No. 602, Seq. Id. No. 603, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618, and Seq. Id. No. 619.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq.
  • a certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
  • a certain embodiment of present invention provides a kit as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 518.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 519.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 520.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 521.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 522.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 523.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 524.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 525.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 526.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 527.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 528.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 529.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 530.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 531.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 532.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 533.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 534.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 535.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 536.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 537.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 538.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 539.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 540.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 541.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 542.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 543.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 544.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 545.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 546.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 547.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 548.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 549.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 550.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 551.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 552.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 553.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 554.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 555.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 556.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 557.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 558.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 559.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 560.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 561.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 562.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 563.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 564.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 565.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 566.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 567.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 568.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 569.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 570.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 571.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 572.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 573.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 574.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 575.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 576.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 577.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 578.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 579.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 580.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 581.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 582.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 583.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 584.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 585.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 586.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 587.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 588.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 589.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 590.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 591.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 592.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 593.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 594.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 595.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 596.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 597.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 598.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 599.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 600.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 601.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 602.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 603.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 604.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 605.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 606.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 607.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 608.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 609.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 610.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 611.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 612.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 613.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 614.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 615.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 616.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 617.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 618.
  • a certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 619.
  • a certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing p53 is measured.
  • a certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
  • a certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising: detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a mutation of exon 19 in the gene encoding EGFR in human tissue.
  • a certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising: detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a deletion of exon 21 in the gene encoding EGFR in human tissue.
  • a certain embodiment of present invention provides erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method as described herein comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
  • a certain embodiment of present invention provides the use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method as described herein.
  • a certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 1 - Seq. Id. No. 15.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 16 - Seq. Id. No. 517.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 518 - Seq. Id. No. 602.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 603 - Seq. Id. No. 619.
  • a certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
  • a certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
  • a certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of
  • Seq. Id. No. 27 Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id.
  • Seq. Id. No. 50 Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id.
  • Seq. Id. No. 241 Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id.
  • Seq. Id. No. 252 Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262,
  • Seq. Id. No. 263 Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id.
  • Seq. Id. No. 274 Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id.
  • Seq. Id. No. 335 Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq.
  • Seq. Id. No. 408 Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No.
  • Seq. Id. No. 426 Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id.
  • Seq. Id. No. 444 Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No.
  • Seq. Id. No. 462 Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id.
  • Seq. Id. No. 480 Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No.
  • Seq. Id. No. 536 Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id.
  • Seq. Id. No. 555 Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No.
  • Seq. Id. No. 22 Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id.
  • Seq. Id. No. 39 Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No.
  • Seq. Id. No. 69 Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id.
  • Seq. Id. No. 98 Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id.
  • Seq. Id. No. 134 Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No.
  • Seq. Id. No. 152 Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id.
  • Seq. Id. No. 170 Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id.
  • Seq. Id. No. 205 Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No.
  • Seq. Id. No. 333 Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No.
  • Seq. Id. No. 389 Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No.
  • Seq. Id. No. 406 Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id.
  • Seq. Id. No. 442 Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
  • a certain embodiment of present invention provides a method as described above, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
  • a certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
  • a certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
  • a certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq.
  • a certain embodiment of present invention provides a method as described above, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
  • a certain embodiment of present invention provides a method as described herein, wherein the treatment is erlotinib.
  • a certain embodiment of present invention provides a method as described herein, wherein the treatment is erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride.
  • Figure 1 Log-transformed values of peptide binding for all peptides grouped by patient (49 samples, 4-digit numbers) and controls (1-digit numbers). Patients have on average higher signals, with a number of antibodies binding to peptides stronger than any signal in control sera.
  • Figure 2 Histogram of distribution of the p-values for the significance of the antibody titers in a Cox regression model of OS or PFS ⁇ EGFR + TRT + EGFR :TRT + SEX+ Antibody titer+ Antibody titer : TRT. If antibody titers do not affect survival, a uniform distribution is expected.
  • Pep - initial peptide selection form Cox- regression model with all covariates RASH: overlapping sequences from peptides predicting PFS (OS) in patients with rash in a proportional hazard model
  • TRT overlapping sequences from peptides predicting PFS (OS) in the erlotinib subgroup
  • EC4 univariate test of response (after 4 cycles, categorical) vs. antibody titer.
  • AIKELREATSPKA 374* SDKDILDEAYVMACA* AIKILREATSPKA 375* SDKDILDEAYVMACG* AIKVLREATSPKA 376* SDKDILDEAYVMACV* ANKDILDEAYVMACA 377* SDKDILDEAYVMAIA* ANKDILDEAYVMACG 378* SDKDILDEAYVMAIG* ANKDILDEAYVMACV 379* SDKDILDEAYVMAIV* ANKDILDEAYVMAIA 380* SDKDILDEAYVMANA* ANKDILDEAYVMAIG 381 * SDKDILDEAYVMANG* ANKDILDEAYVMAIV 382* SDKDILDEAYVMANV* ANKDILDEAYVMANA 383* SDKDILDEAYVMASA* ANKDILDEAYVMASA* ANKDILDEAYVMASA* ANKDILDEAYVMANG 384* SDKDILDEAYVMASG* ANKDILDEAYVMANV
  • Peptide arrays were created by PepStarTM (JPT Peptide Technologies GmbH, Berlin, Germany) peptide microarray platform to generate customized peptide microarrays on glass slides for biomarker discovery, immunomonitoring and detection and validation of protein interactions. Peptides are immobilized on glass slides via a flexible linker. Chemoselective coupling generates microarrays of directed and covalently attached peptides.
  • TASK was a 200- patient randomized, open label, Phase II study of Tarceva® in combination with Avastin® (bevazizumab) compared to standard chemotherapy regimens (gemcitabine plus cisplatin or paclitaxel plus carboplatin) plus Avastin® in first-line NSCLC patients. Further enrollment on this study was halt after data from a pre-planned interim analysis of the first 120 patients. Occurrence of rash was recorded as adverse event. Biopsies from all patients were tested for the occurrence of EGFR mutations and the mutation status has been recorded.

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Abstract

The invention generally relates to biomarkers associated with NSCLC, and methods and compositions for the detection and diagnosis of non-small cell lung cancer in a human subject.

Description

AUTOIMMUNE ANTIBODIES
Field of the invention
The present invention provides methods for identifying patients diagnosed with non-small cell lung cancer who will most benefit from treatment with erlotinib comprising detecting autoantibodies in blood serum of said patients.
Background of the invention
Tarceva® is an orally active, potent, inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase (TKI).
Erlotinib hydrochloride is the active ingredient in Tarceva®, which is approved as single agent treatment for patients with advanced non- small cell lung cancer (NSCLC) after treatment with chemotherapy, as maintenance treatment for patients not progressing during chemotherapy (1st line maintenance) or after failure of chemotherapy (2nd /3rd line maintenance). Tarceva® is also approved as first line treatment for patients whose tumor harbors an EGFR activating mutation in the EU. Expression of unusual proteins is common in cancer and viral infection. The mammalian immune system contains a specialized arm that recognizes proteins induced by cellular transformation (neo-antigens) and effectively eliminates cells that express these neo-antigens against which tolerance has not established during development. This arm of the immune system is thought to be effective against viral infections, spontaneous chromosomal and genomic rearrangements caused by errors of the cell division machinery, or carcinogen-induced transforming mutations. While the initial cytotoxic immune response - which is mediated by the recognition of the unusual proteins displayed on MHCI complexes by CD8+ T-cells - is fast and effective, a sustained response against virus infections or aberrant cellular clones requires the co- stimulatory effect of CD4+ T-helper cells which are activated after presentation of extracellular peptides (which can stem from cells lysed in the first phase of the cytotoxic immune response) via MHCII complexes of professional antigen presenting cells. Additionally, these cells are able to induce a lasting B-cell response and antibodies to viral or aberrant proteins. The infiltration of a tumor with large numbers of CD8+ T-cells has shown to be a better prognostic marker than traditional tumor staging in colorectal cancer (Koizumi, Hojo et al. 2007 !), and it has been associated with favorable prognosis in almost all major solid carcinomas independently of cancer cell type. Autoantibodies are well known diagnostic entities in cancer. Many cancer autoantibodies are proteins that are normally expressed in embryonic tissues and therefore represent a "foreign" protein against which immune tolerance is not established. The shedding of these proteins to the bloodstream late in cancer history leads to a humoral immune response. A typical example is the common cancer marker CEA (cancer embryonic antigen). Tumors frequently exhibit faulty protein processing. Prominent examples include proteins that are incorrectly cleaved by cell localization proteases (the presence of autoantibodies against the N-terminal sequence of p53 which is normally cleaved after the protein is targeted to the nucleus is one of the most specific biomarkers of lung cancer) or incorrectly glycosylated by cellular glycosylases (anti-MUCl- antibodies against a form of MUC1 that is incorrectly O-glycosylated is a biomarker for a variety of cancers). Even though p53 mutations are frequently observed in tumors, the specificity of the autoantibodies against this protein is almost always against the N-terminus of the protein - connecting the immunogenicity of p53 more to the ectopic expression of a protein that is normally short lived and located in the nucleus. The detection of natural EGFR autoantibodies in serum of NSCLC patients has been described by Li et al.2. Li et al. 3 and Chapman et al.4 described the detection of natural autoantibodies to p53, HER2, NY-ESO-1, CAGE, MUC1 and GBU4-5. Further, WO20110739055 relates to tumor markers associated with the progression of a cancer disease from a less progressed stage to a more progressed stage. Unusual (mutated or expressed in abnormal quantities or locations) tumor proteins can invoke an antibody response. Tumor-induced autoantibodies have frequently been observed and their utility as diagnostic markers has been investigated (Albert and Darnell 20046). While autoantibodies to tumor proteins can be found that have exquisite specificity, most of them lack the required sensitivity for a diagnostic test. Few reliable epidemiologic and genetic markers that predict erlotinib hydrochloride response are known in the art. In particular, EGFR mutations in exon 18-21 (intracellular kinase domain of the receptor) were described to be linked with better prognosis as well as with better response to TKI treatment (Paz-Ares, Soulieres et al. 20107). The only predictive marker currently known (EGFR activating mutation) is difficult to diagnose as a biopsy of the tumor is needed. At present only about 50% of NSCLC patients are diagnosed with a biopsy (Reck, Hermes et al. 201 Is). There is a definite need for simpler techniques to detect predictive markers of TKI efficacy. It is desirable to identify the responders at diagnosis in order to have as many patients as possible benefiting from erlotinib treatment as early as possible, while exploring other treatment options for patients not likely to respond.
Detailed description of the invention Present invention solves that problem in that it provides a method of diagnosis of cancer in a human subject.
Present invention solves that problem in that it provides a method of diagnosis of non- small cell lung cancer in a human subject. Present invention solves that problem in that it provides a method of diagnosis of non- small cell lung cancer in a human subject by providing antibodies against mutated EGFR sequences.
A patient identified by a method as described herein is a patient, in particular a NSCLC patient who will respond to the treatment with erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride.
We sursprisingly found that present autoantibodies possess the required sensitivity for a diagnostic test, especially autoantibodies against mutated EGFR sequences.
EGFR is normally bound to the cell membrane and not shed to the bloodstream. EGFR is a normal adult protein that is found in large quantities in some adult tissues. Immune tolerance is expected to be established against this protein and many of its variants. Almost all of the sequences belong to the cytoplasmic part of the molecule and are invisible to professional antigen presenting cells. The mutations affect only a small part of the EGFR molecule.
Unless defined otherwise, all terms used herein have the same meanings as commonly understood by a skilled artisan to which art this invention belongs. The term "a level of said autoantibody representative for a human subject of a healthy population" refers to an estimate of the mean level of the autoantibody in serum of a population of patients who do not suffer from NSCLC.
The term "a level of said autoantibody representative for a NSCLC patient" refers to an estimate of the mean level of the autoantibody in serum of a population of patients who suffer from NSCLC.
The term "overall survival (OS)" refers to the length of time from diagnosis of disease during and after treatment the patient survives. As the skilled person will appreciate, a patient's overall survival is improved or enhanced, if the patient belongs to a subgroup of patients that has a statistically significant longer mean survival time as compared to another subgroup of patients. The term "progression-free survival (PFS)" refers to the length of time from diagnosis of disease during and after treatment during which, according to the assessment of the treating physician or investigator, the patient's disease does not become worse, i.e., does not progress. As the skilled person will appreciate, a patient's progression- free survival is improved or enhanced if the patient belongs to a subgroup of patients that has a longer length of time during which the disease does not progress as compared to the average or mean progression free survival time of a control group of similarly situated patients.
The term "patient" refers to any single mammal for which treatment is desired. In particular, the "patient" is a human subject. More particularly, the patient is a human subject suffering from cancer, in particular NSCLC.
The term "autoantibody" is a type of protein manufactured by the immune system of a patient that is directed against one or more of the patient's own proteins.
The term "amino acid" denotes the group of naturally occurring carboxy a-amino acids comprising alanine (three letter code: ala, one letter code: A), arginine (arg, R), asparagine (asn, N), aspartic acid (asp, D), cysteine (cys, C), glutamine (gin, Q), glutamic acid (glu, E), glycine (gly, G), histidine (his, H), isoleucine (ile, I), leucine (leu, L), lysine (lys, K), methionine (met, M), phenylalanine (phe, F), proline (pro, P), serine (ser, S), threonine (thr, T), tryptophan (trp, W), tyrosine (tyr, Y), and valine (val, V). As used herein, "therapy" or "treatment" (and grammatical variations thereof such as
"treat" or "treating") refers to clinical intervention in an attempt to alter the natural course of a disease in the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.
The term "gene" as used herein comprises variants of the gene. The term "variant" relates to nucleic acid sequences which are substantially similar to the nucleic acid sequences given by the GenBank accession number. The term "substantially similar" is well understood by a person skilled in the art. In particular, a gene variant may be an allele which shows nucleotide exchanges compared to the nucleic acid sequence of the most prevalent allele in the human population. Preferably, such a substantially similar nucleic acid sequence has a sequence similarity to the most prevalent allele of at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%. The term "variants" is also meant to relate to splice variants.
The term "mutation" refers to changes in a genomic sequence. These random sequences can be defined as sudden and spontaneous changes in the cell. Mutation can result in several different types of change in sequences; these can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. The term "somatic mutation" refers to a change in the genetic structure that is neither inherited nor passed to offspring.
The phrase "recommending a treatment" as used herein refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to identify the patient as suitably treated or not suitably treated with a therapy. In some embodiment the therapy may comprise a drug. The information or data may be in any form, written, oral or electronic. In some embodiments, using the information or data generated includes communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof. In some embodiments, communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof. In some further embodiments, communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional. In some embodiments, the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level. In some embodiments, the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample. In some embodiments, the information or data includes an indication that the patient is suitably treated or not suitably treated with a therapy comprising said drug. In some embodiments, the therapy is erlotinib.
The phrase "providing a diagnosis" as used herein refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to diagnose a disease in the patent. The information or data may be in any form, written, oral or electronic. In some embodiments, using the information or data generated includes presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof. In some embodiments, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof. In some embodiments, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional. In some embodiments, the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level. In some embodiments, the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample. In some embodiments, the information or data includes an indication that the patient is diagnosed with said disease. In some embodiments, said disease is non-small cell lung cancer.
During the TASK study, biopsy material had been collected and the tumor cells have been tested for the presence of the most frequent somatic mutations, i.e. a deletion at exon 19, and a point mutation at exon 21. During the TASK study serum samples had been collected at various time points (pre-dose, day 8, day 22 and progression) from all patients and were assessed for autoantibodies against EGFR.
In these patients, autoantigenic peptide sequences that predict development of rash, or prolonged progression free or overall survival inevitably include a set of sequences that are derived from the EGFR sequence starting at position 737 and extending through 756. These peptides include a number of sequence variants, but inevitably include sequences that have a deletion at position 746-750 or close nearby (Table 2).
This corresponds exactly to the position of the deletion in the exon 19 somatic mutation, known to be predictive for outstanding efficacy from treatment with TKI (Rosell et al. 20099, Mok et al 200910).
The presence of a somatic EGFR mutation in exon 19 in tumor tissue leads to protein variant against that the immune system has not developed tolerance. The somatic mutation occurs only in the tumor, and therefore, if it induces an autoantibody which can be detected in the patient's serum it can be used to draw conclusions about the presence of an exon 19 mutation or exon 21 mutation in the NSCLC tissue, which is well known to predict increased progression free survival and superiority of tyrosine kinase monotherapy over chemotherapy (Heigener and Reck 201111).
The autoantibody can be detected using a standard blood sample from the patient without the need to obtain tumor cells with a biopsy. This is a large advantage over the current practice, as recovery rates of useful tumor samples even in clinical studies do not exceed 50% (Reck, Hermes et al. 201112).
Anti-EGFR autoantibodies can be detected in blood samples of NSCLC patients at higher concentrations than in healthy controls (Figure 1). In particular, peptide sequences have been identified that yield consecutive regions of high immunogenicity with large differences between patient and healthy controls sera. Consecutive sequence stretches were identified, where ratios of individual peptide signals in more than 30% of the cancer patients to maximum value in controls was larger than 8 (Table 1).
Protein Sequence Consensus sequence of autoantigenic peptides in the region
Region
EGFR 323-336 VRKSKKSEGPSxKV
EGFR 546-564 PREFVENSECIQCHPECL
EGFR 574-591 RGPDNCIQCAHYIDGPHCVKTCP
EGFR 735-762 Del 1 GEKVKIPVAIK[-S]PKANK
EGFR 739-758 Del 2 KIPVAIK[-HRK]PTSPK
EGFR 793-806 MPFGCLLDYVREH
EGFR 867-883 KEYHAEGGKVPIKWM EGFR 986-1002 RMHLPSPTDSNFYRA
EGFR 1081-1095 SIDDTFLPVPEYIN
EGFR 1148-1166 NSTFDSPAHWAQKGSHQI
Table 1 : Consecutive EGFR sequences with high auto antigenicity in NLSCL patients
The above sequences can be used for the early diagnosis of NSCLC.
Regression analysis has identified significant evidence that the presence of antibodies to the peptides influence both, progression free survival (PFS) and overall survival (OS) (Figure 2). Although the number of samples is small in comparison to the number of peptides, many covariates need to be considered and none of the individual peptides reach sufficient statistical significance, we surprisingly found that when combining overlapping information from various independent statistical approaches, selection of a relevant peptide from the many candidates obtained after univariate analysis is possible. Figure 3 illustrates the process that led to selection of the candidate sequences listed in Table 2. Sequences listed in Table 2 or any continuous subsequences thereof longer than 8 amino acids are candidate sequences.
Figure imgf000008_0001
Table 2: Antigenic sequences influencing PFS and OS of NSCLC patients
KVKIPVAIKELREATSPKA Annotation
KVKIPVAIK APKA 737 V003
KVKIPVAIK— APTS 737 V004
KVKIPVAIKD PKA 737 V007
KVKIPVAIKELKA 737 V015
KVKIPVAIKE PKA 737 V019
KVKIPVAIKEQKA 737 V024
KVKIPVAIKE SKA 737 V029
KVKIPVAIKEV PK 737 V037
KVKIPVAIK IPKA 737 V039 KVKIPVAIK SPKA 737 V054
KVKIPVAIK TPKA 737 V057
--KIPVAIKE— ASPKA 739 V010
--KIPVAIKEF— SPKA 739 V013
--KIPVAIKE— SPKA 739 V027
--KIPVAIK— VASPKA 739 V067
--KIPVAIK— VPSPKA 739 V070
Table 3: Examples for peptide sequences with high predictive potential for prolonged
progression free survival in patients with EGFR mutations that develop rash
EGFR peptide sequences selected from Seq. Id. No. 1 - Seq. Id. No. 15 are consecutive sequences with high auto antigenicity in NLSCL patients. EGFR peptide sequences selected from Seq. Id. No. 16 - Seq. Id. No. 517 are useful for predicting the occurrence and grade of adverse events like rash to erlotinib treatment.
EGFR peptide sequences selected from Seq. Id. No. 518 - Seq. Id. No. 602 are antigenic sequences influencing, in particular extending, progression free and overall survival of NSCLC patients, in particular mutated EGFR peptide sequences Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559 and Seq. Id. No. 560, as well as EGFR peptide sequences Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521 and Seq. Id. No.561.
EGFR peptide sequences selected from Seq. Id. No. 603 - Seq. Id. No. 619 have high predictive potential for prolonged progression free survival in patients with EGFR mutations that develop rash.
Antibodies against these peptide sequences most likely influence PFS and OS if they are present in patients. Tests that detect the presence of these antibodies in patient sera could be used to guide treatment and stratify patients into treatment groups.
Present onvention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing mutated human EGFR is measured. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. 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No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 601, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No.
21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id.
No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq.
Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No.
44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id.
No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq.
Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61,
Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id.
No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq.
Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85,
Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No.
91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103,
Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id.
No. 109, Seq. Id. No. 110, Seq. Id. No. I l l, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114,
Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id.
No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id.
No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136,
Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id.
No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147,
Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158,
Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id.
No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169,
Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id.
No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id.
No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191,
Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id.
No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202,
Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213,
Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id.
No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224,
Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id.
No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619..
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560. A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
A certain embodiment of present invention provides erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method as described herein comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
A certain embodiment of present invention provides the use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method as described herein.
A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No.
68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id.
No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq.
Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No.
91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id.
No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103,
Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id.
No. 109, Seq. Id. No. 110, Seq. Id. No. I l l, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id.
No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125,
Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id.
No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136,
Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147,
Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id.
No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158,
Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id.
No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id.
No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180,
Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id.
No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191,
Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202,
Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id.
No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213,
Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id.
No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id.
No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235,
Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id.
No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246,
Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257,
Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id.
No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268,
Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id.
No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517. A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560. A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer , in particular wherein the level of an autoantibody recognizing human EGFR is measured
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide is selected from the group consisting of Seq. Id.
No. 1, Seq. Id. No. 2, Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13,
Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No.
19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id.
No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq.
Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No.
42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id.
No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq.
Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59,
Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 64, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id.
No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq.
Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82,
Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No.
88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq.
Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 102, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No.
105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110,
Seq. Id. No. I l l, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id.
No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id.
No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132,
Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id.
No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143,
Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154,
Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id.
No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165,
Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id.
No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. 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No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 525, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 561, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 566, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 600, Seq. Id. No. 601, Seq. Id. No. 602, Seq. Id. No. 603, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618, and Seq. Id. No. 619.
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
A certain embodiment of present invention provides a kit as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 518. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 519.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 520. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 521.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 522. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 523.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 524.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 525.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 526.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 527. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 528.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 529.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 530.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 531.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 532. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 533.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 534.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 535. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 536.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 537. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 538.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 539.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 540.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 541.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 542. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 543.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 544.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 545.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 546.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 547. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 548.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 549.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 550. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 551.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 552. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 553.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 554.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 555.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 556.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 557. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 558.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 559.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 560.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 561.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 562. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 563.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 564.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 565. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 566.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 567. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 568.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 569.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 570.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 571.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 572. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 573.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 574.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 575.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 576.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 577. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 578.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 579.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 580. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 581.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 582. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 583.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 584.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 585.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 586.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 587. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 588.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 589.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 590.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 591.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 592. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 593.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 594.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 595. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 596.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 597. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 598.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 599.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 600.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 601.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 602. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 603.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 604.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 605.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 606.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 607. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 608.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 609.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 610. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 611.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 612. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 613.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 614.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 615.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 616.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 617. A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 618.
A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 619.
A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing p53 is measured.
A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
A certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising: detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a mutation of exon 19 in the gene encoding EGFR in human tissue. A certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising: detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a deletion of exon 21 in the gene encoding EGFR in human tissue.
A certain embodiment of present invention provides erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method as described herein comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
A certain embodiment of present invention provides the use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method as described herein.
A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 1 - Seq. Id. No. 15. A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 16 - Seq. Id. No. 517.
A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 518 - Seq. Id. No. 602.
A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 603 - Seq. Id. No. 619. A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of
Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20,
Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No.
26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id.
No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq.
Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No.
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A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15. A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No.
21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id.
No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38,
Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No.
44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id.
No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq.
Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No.
68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id.
No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq.
Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. 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No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517. A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
A certain embodiment of present invention provides a method as described above, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population. A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
A certain embodiment of present invention provides a method as described above, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
A certain embodiment of present invention provides a method as described herein, wherein the treatment is erlotinib.
A certain embodiment of present invention provides a method as described herein, wherein the treatment is erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride.
Figures and Seq. Id. Numbers
Figure 1 : Log-transformed values of peptide binding for all peptides grouped by patient (49 samples, 4-digit numbers) and controls (1-digit numbers). Patients have on average higher signals, with a number of antibodies binding to peptides stronger than any signal in control sera. Figure 2: Histogram of distribution of the p-values for the significance of the antibody titers in a Cox regression model of OS or PFS ~ EGFR + TRT + EGFR :TRT + SEX+ Antibody titer+ Antibody titer : TRT. If antibody titers do not affect survival, a uniform distribution is expected. The deviation from the uniform distribution is highly significant, which lead to the conclusion that approximately 50% of the 245 antibody titers with p-values < 0.05 will have a significant influence on progression free survival. A similar model calculation for overall survival (OS) yields 663 candidates at p-Values < 0.05 with a slightly better false discovery rate of approximately 40%. Figure 3: Venn diagrams illustrating the refinement of peptide candidates for (A) progression free survival and (B) overall survival. Pep - initial peptide selection form Cox- regression model with all covariates; RASH: overlapping sequences from peptides predicting PFS (OS) in patients with rash in a proportional hazard model; TRT: overlapping sequences from peptides predicting PFS (OS) in the erlotinib subgroup; EC4: univariate test of response (after 4 cycles, categorical) vs. antibody titer.
Figure 4: Presence of autoantibodies against a mutated EGFR peptide predicts (p=0.006) a better treatment outcome in the Tarceva® arm of the trial independent of the occurrence of rash.
Seq. Seq. Id.
protein sequence protein sequence
Id. No. No.
1 * GEKVKIPVAIKPKANK 311 * KVKIPVAIATSPKA
2* GEKVKIPVAIKSPKANK 312* KVKIPVAIEAPSPKA
3 KEYHAEGGKVPIKWM 313* KVKIPVAIEATSPKA
4* KIPVAIKHPTSPK 314* KVKIPVAIEEAPSPKA
5* KIPVAIKKPTSPK 315* KVKIPVAIEEATSPKA
6* KIPVAIKPTSPK 316* KVKIPVAIEEPSPKA
KIPVAIKRPTSPK 317* KVKIPVAIEETSPKA
8 MPFGCLLDYVREH 318* KVKIPVAIEPSPKA
9 NSTFDSPAHWAQKGSHQI 319* KVKIPVAIERAPSPKA
10 PREFVENSECIQCHPECL 320* KVKIPVAIERATSPKA
11 RGPDNCIQCAHYIDGPHCVKTCP 321 * KVKIPVAIEREAPSPKA
12 RMHLPSPTDSNFYRA 322* KVKIPVAIEREATSPKA
13 SIDDTFLPVPEYIN 323* KVKIPVAIEREPSPKA
14 VRKCK CEGPCRKV 324* KVKIPVAIERETSPKA
15* VRKSK SEGPSRKV 325* KVKIPVAIERPSPKA
16* ADKDILDEAYVMACA 326* KVKIPVAIERTSPKA
17* ADKDILDEAYVMACG 327* KVKIPVAIETSPKA
18* ADKDILDEAYVMACV 328* KVKIPVAIKAPSPKA
19* ADKDILDEAYVMAIA 329* KVKIPVAIKATSPKA
20* ADKDILDEAYVMAIG 330* KVKIPVAIKEAPSPKA
21 * ADKDILDEAYVMAIV 331 * KVKIPVAIKEATSPKA
22* ADKDILDEAYVMANA 332* KVKIPVAIKEEAPSPKA
23* ADKDILDEAYVMANG 333* KVKIPVAIKEEATSPKA
24* ADKDILDEAYVMANV 334* KVKIPVAIKEEPSPKA
25* ADKDILDEAYVMASA 335* KVKIPVAIKEETSPKA
26* ADKDILDEAYVMASG 336* KVKIPVAIKEPSPKA
27* ADKDILDEAYVMASV 337* KVKIPVAIKERAPSPKA
28* ADKDILDEAYVMTCA 338* KVKIPVAIKERATSPKA
29* ADKDILDEAYVMTCG 339* KVKIPVAIKEREAPSPKA
30* ADKDILDEAYVMTCV 340* KVKIPVAIKEREATSPKA
31 * ADKDILDEAYVMTIA 341 * KVKIPVAIKEREPSPKA
32* ADKDILDEAYVMTIG 342* KVKIPVAIKERETSPKA
33* ADKDILDEAYVMTIV 343* KVKIPVAIKERPSPKA
34* ADKDILDEAYVMTNA 344* KVKIPVAIKERTSPKA
35* ADKDILDEAYVMTNG 345* KVKIPVAIKETSPKA
36* ADKDILDEAYVMTNV 346* KVKIPVAIKPSPKA * ADKDILDEAYVMTSA 347* KVKIPVAIKRAPSPKA* ADKDILDEAYVMTSG 348* KVKIPVAIKRATSPKA* ADKDILDEAYVMTSV 349* KVKIPVAIKREAPSPKA* ADKEILDEAYVMACA 350* KVKIPVAIKREATSPKA* ADKEILDEAYVMACG 351 * KVKIPVAIKREPSPKA* ADKEILDEAYVMACV 352* KVKIPVAIKRETSPKA* ADKEILDEAYVMAIA 353* KVKIPVAIKRPSPKA* ADKEILDEAYVMAIG 354* KVKIPVAIKPvTSPKA* ADKEILDEAYVMAIV 355* KVKIPVAIKTSPKA* ADKEILDEAYVMANA 356* KVKIPVAIPSPKA* ADKEILDEAYVMANG 357* KVKIPVAIRAPSPKA* ADKEILDEAYVMANV 358* KVKIPVAIRATSPKA* ADKEILDEAYVMASA 359* KVKIPVAIREAPSPKA* ADKEILDEAYVMASG 360* KVKIPVAIREATSPKA* ADKEILDEAYVMASV 361 * KVKIPVAIREPSPKA* ADKEILDEAYVMTCA 362* KVKIPVAIRETSPKA* ADKEILDEAYVMTCG 363* KVKIPVAIRPSPKA* ADKEILDEAYVMTCV 364* KVKIPVAIRTSPKA* ADKEILDEAYVMTIA 365* KVKIPVAITSPKA* ADKEILDEAYVMTIG 366* LREEILDEAYVMA* ADKEILDEAYVMTIV 367* LREPILDEAYVMA* ADKEILDEAYVMTNA 368* PEGEKAKIPVAIKELREA* ADKEILDEAYVMTNG 369* PEGEKAKIPVAIRELREA* ADKEILDEAYVMTNV 370 PEGEKVKIPVAIKELREA* ADKEILDEAYVMTSA 371 * PEGEKVKIPVAIRELREA* ADKEILDEAYVMTSG 372* RLLVHRDLAARNV* ADKEILDEAYVMTSV 373 RRLVHRDLAARNV
AIKELREATSPKA 374* SDKDILDEAYVMACA* AIKILREATSPKA 375* SDKDILDEAYVMACG* AIKVLREATSPKA 376* SDKDILDEAYVMACV* ANKDILDEAYVMACA 377* SDKDILDEAYVMAIA* ANKDILDEAYVMACG 378* SDKDILDEAYVMAIG* ANKDILDEAYVMACV 379* SDKDILDEAYVMAIV* ANKDILDEAYVMAIA 380* SDKDILDEAYVMANA* ANKDILDEAYVMAIG 381 * SDKDILDEAYVMANG* ANKDILDEAYVMAIV 382* SDKDILDEAYVMANV* ANKDILDEAYVMANA 383* SDKDILDEAYVMASA* ANKDILDEAYVMANG 384* SDKDILDEAYVMASG* ANKDILDEAYVMANV 385* SDKDILDEAYVMASV* ANKDILDEAYVMASA 386* SDKDILDEAYVMTCA* ANKDILDEAYVMASG 387* SDKDILDEAYVMTCG* ANKDILDEAYVMASV 388* SDKDILDEAYVMTCV* ANKDILDEAYVMTCA 389* SDKDILDEAYVMTIA* ANKDILDEAYVMTCG 390* SDKDILDEAYVMTIG* ANKDILDEAYVMTCV 391 * SDKDILDEAYVMTIV* ANKDILDEAYVMTIA 392* SDKDILDEAYVMTNA* ANKDILDEAYVMTIG 393* SDKDILDEAYVMTNG* ANKDILDEAYVMTIV 394* SDKDILDEAYVMTNV* ANKDILDEAYVMTNA 395* SDKDILDEAYVMTSA* ANKDILDEAYVMTNG 396* SDKDILDEAYVMTSG 87* ANKDILDEAYVMTNV 397* SDKDILDEAYVMTSV
88* ANKDILDEAYVMTSA 398* SDKEILDEAYVMACA
89* ANKDILDEAYVMTSG 399* SDKEILDEAYVMACG
90* ANKDILDEAYVMTSV 400* SDKEILDEAYVMACV
91 * ANKEILDEAYVMACA 401 * SDKEILDEAYVMAIA
92* ANKEILDEAYVMACG 402* SDKEILDEAYVMAIG
93* ANKEILDEAYVMACV 403* SDKEILDEAYVMAIV
94* ANKEILDEAYVMAIA 404* SDKEILDEAYVMANA
95* ANKEILDEAYVMAIG 405* SDKEILDEAYVMANG
96* ANKEILDEAYVMAIV 406* SDKEILDEAYVMANV
97* ANKEILDEAYVMANA 407* SDKEILDEAYVMASA
98* ANKEILDEAYVMANG 408* SDKEILDEAYVMASG
99* ANKEILDEAYVMANV 409* SDKEILDEAYVMASV
100* ANKEILDEAYVMASA 410* SDKEILDEAYVMTCA
101 * ANKEILDE AY VM AS G 411 * SDKEILDEAYVMTCG
102 ANKEILDEAYVMASV 412* SDKEILDEAYVMTCV
103* ANKEILDEAYVMTCA 413* SDKEILDEAYVMTIA
104* ANKEILDEAYVMTCG 414* SDKEILDEAYVMTIG
105* ANKEILDEAYVMTCV 415* SDKEILDEAYVMTIV
106* ANKEILDEAYVMTIA 416* SDKEILDEAYVMTNA
107* ANKEILDEAYVMTIG 417* SDKEILDEAYVMTNG
108* ANKEILDEAYVMTIV 418* SDKEILDEAYVMTNV
109* ANKEILDEAYVMTNA 419* SDKEILDEAYVMTSA
110* ANKEILDEAYVMTNG 420* SDKEILDEAYVMTSG
111 * ANKEILDEAYVMTNV 421 * SDKEILDEAYVMTSV
112* ANKEILDEAYVMTSA 422* SNKDILDEAYVMACA
113* ANKEILDE AY VMT S G 423* SNKDILDEAYVMACG
114* ANKEILDE AY VMT S V 424* SNKDILDEAYVMACV
115* ASKDILDEAYVMACA 425* SNKDILDEAYVMAIA
116* ASKDILDEAYVMACG 426* SNKDILDEAYVMAIG
117* AS KDILDE AY VM AC V 427* SNKDILDEAYVMAIV
118* AS KDILDE AY VM AI A 428* SNKDILDEAYVMANA
119* ASKDILDEAYVMAIG 429* SNKDILDEAYVMANG
120* AS KDILDE AY VMAIV 430* SNKDILDEAYVMANV
121 * ASKDILDEAYVMANA 431 * SNKDILDEAYVMASA
122* ASKDILDEAYVMANG 432* SNKDILDE AY VM AS G
123* AS KDILDE AY VM AN V 433* SNKDILDEAYVMASV
124* ASKDILDEAYVMASA 434* SNKDILDEAYVMTCA
125* AS KDILDE AY VM AS G 435* SNKDILDEAYVMTCG
126* AS KDILDE AY VM AS V 436* SNKDILDEAYVMTCV
127* ASKDILDEAYVMTCA 437* SNKDILDEAYVMTIA
128* ASKDILDEAYVMTCG 438* SNKDILDEAYVMTIG
129* ASKDILDEAYVMTCV 439* SNKDILDEAYVMTIV
130* AS KDILDE AY VMTI A 440* SNKDILDEAYVMTNA
131 * ASKDILDEAYVMTIG 441 * SNKDILDEAYVMTNG
132* AS KDILDE AY VMTI V 442* SNKDILDEAYVMTNV
133* ASKDILDEAYVMTNA 443* SNKDILDE AY VMT S A
134* AS KDILDE AY VMTNG 444* SNKDILDE AY VMT S G
135* AS KDILDE AY VMTNV 445* SNKDILDE AY VMT S V
136* AS KDILDE AY VMT S A 446* SNKEILDEAYVMACA 137* AS KDILDE AY VMT S G 447* SNKEILDEAYVMACG
138* AS KDILDE AY VMT S V 448* SNKEILDEAYVMACV
139* AS KEILDE AY VM AC A 449* SNKEILDEAYVMAIA
140* ASKEILDEAYVMACG 450* SNKEILDEAYVMAIG
141 * AS KEILDE AY VM AC V 451 * SNKEILDEAYVMAIV
142* AS KEILDE AY VM AI A 452* SNKEILDEAYVMANA
143* ASKEILDEAYVMAIG 453* SNKEILDEAYVMANG
144* AS KEILDE AY VMAIV 454* SNKEILDEAYVMANV
145* AS KEILDE AY VM AN A 455* SNKEILDEAYVMASA
146* AS KEILDE AY VMANG 456* SNKEILDE AY VM AS G
147* AS KEILDE AY VM AN V 457* SNKEILDEAYVMASV
148* ASKEILDEAYVMASA 458* SNKEILDEAYVMTCA
149* AS KEILDE AY VM AS G 459* SNKEILDEAYVMTCG
150* AS KEILDE AY VM AS V 460* SNKEILDEAYVMTCV
151 * ASKEILDEAYVMTCA 461 * SNKEILDEAYVMTIA
152* ASKEILDEAYVMTCG 462* SNKEILDEAYVMTIG
153* ASKEILDEAYVMTCV 463* SNKEILDEAYVMTIV
154* AS KEILDE AY VMTI A 464* SNKEILDEAYVMTNA
155* ASKEILDEAYVMTIG 465* SNKEILDEAYVMTNG
156* AS KEILDE AY VMTI V 466* SNKEILDEAYVMTNV
157* AS KEILDE AY VMTN A 467* SNKEILDEAYVMTSA
158* AS KEILDE AY VMTNG 468* SNKEILDE AY VMT S G
159* AS KEILDE AY VMTN V 469* SNKEILDE AY VMT S V
160* ASKEILDEAYVMTSA 470* SSKDILDEAYVMACA
161 * AS KEILDE AY VMT S G 471 * SSKDILDEAYVMACG
162* AS KEILDE AY VMT S V 472* SSKDILDEAYVMACV
163* CLLVHRDLAARNV 473* SSKDILDEAYVMAIA
164* CRLVHRDLAARNV 474* SSKDILDEAYVMAIG
165* DDKDILDEAYVMACA 475* SSKDILDEAYVMAIV
166* DDKDILDEAYVMACG 476* SSKDILDEAYVMANA
167* DDKDILDEAYVMACV 477* SSKDILDEAYVMANG
168* DDKDILDEAYVMAIA 478* S SKDILDE AYVM ANV
169* DDKDILDEAYVMAIG 479* SSKDILDEAYVMASA
170* DDKDILDEAYVMAIV 480* SSKDILDEAYVMASG
171 * DDKDILDEAYVMANA 481 * S SKDILDE AYVM AS V
172* DDKDILDEAYVMANG 482* S SKDILDE AYVMTC A
173* DDKDILDEAYVMANV 483* S SKDILDE AYVMTCG
174* DDKDILDEAYVMASA 484* S SKDILDE AYVMTCV
175* DDKDILDEAYVMASG 485* S SKDILDE AYVMTI A
176* DDKDILDEAYVMASV 486* S SKDILDE AYVMTIG
177* DDKDILDEAYVMTCA 487* S SKDILDE AYVMTI V
178* DDKDILDEAYVMTCG 488* S SKDILDE AYVMTN A
179* DDKDILDEAYVMTCV 489* S SKDILDE AYVMTNG
180* DDKDILDEAYVMTIA 490* S SKDILDE AYVMTNV
181 * DDKDILDEAYVMTIG 491 * SSKDILDEAYVMTSA
182* DDKDILDEAYVMTIV 492* SSKDILDEAYVMTSG
183* DDKDILDEAYVMTNA 493* SSKDILDEAYVMTSV
184* DDKDILDEAYVMTNG 494* SSKEILDEAYVMACA
185* DDKDILDEAYVMTNV 495* SSKEILDEAYVMACG
186* DDKDILDEAYVMTSA 496* SSKEILDEAYVMACV 187* DDKDILDEAYVMTSG 497* SSKEILDEAYVMAIA
188* DDKDILDEAYVMTSV 498* SSKEILDEAYVMAIG
189* DDKEILDEAYVMACA 499* SSKEILDEAYVMAIV
190* DDKEILDEAYVMACG 500* SSKEILDEAYVMANA
191 * DDKEILDEAYVMACV 501 * SSKEILDEAYVMANG
192* DDKEILDEAYVMAIA 502* SSKEILDEAYVMANV
193* DDKEILDEAYVMAIG 503* SSKEILDEAYVMASA
194* DDKEILDEAYVMAIV 504* SSKEILDEAYVMASG
195* DDKEILDEAYVMANA 505* SSKEILDEAYVMASV
196* DDKEILDEAYVMANG 506* SSKEILDEAYVMTCA
197* DDKEILDEAYVMANV 507* SSKEILDEAYVMTCG
198* DDKEILDEAYVMASA 508* SSKEILDEAYVMTCV
199* DDKEILDE AY VM AS G 509* SSKEILDEAYVMTIA
200* DDKEILDEAYVMASV 510* SSKEILDEAYVMTIG
201 * DDKEILDEAYVMTCA 511 * SSKEILDEAYVMTIV
202* DDKEILDEAYVMTCG 512* SSKEILDEAYVMTNA
203* DDKEILDEAYVMTCV 513* SSKEILDEAYVMTNG
204* DDKEILDEAYVMTIA 514* SSKEILDEAYVMTNV
205* DDKEILDEAYVMTIG 515* SSKEILDEAYVMTSA
206* DDKEILDEAYVMTIV 516* SSKEILDEAYVMTSG
207* DDKEILDEAYVMTNA 517* SSKEILDEAYVMTSV
208* DDKEILDEAYVMTNG 518* AVVMASVDNPHVCR
209* DDKEILDEAYVMTNV 519 AYVMASVDNPHVCR
210* DDKEILDEAYVMTSA 520 CTGPGLEGCPTNG
211 * DDKEILDE AY VMT S G 521 DEAYVMASVDNPHVCRLLG
212* DDKEILDE AY VMT S V 522* ILKETEFKKIFVLGPGAFGT
213* DNKDILDEAYVMACA 523* ILKETEFKKIFVLGSGAFGT
214* DNKDILDEAYVMACG 524* ILKETEFKKIKVLGPGAFGT
215* DNKDILDEAYVMACV 525 ILKETEFKKIKVLGSGAFGT
216* DNKDILDEAYVMAIA 526* ILKETEFKKLFVLGPGAFGT
217* DNKDILDEAYVMAIG 527* ILKETEFKKLFVLGSGAFGT
218* DNKDILDEAYVMAIV 528* ILKETEFKKLKVLGPGAFGT
219* DNKDILDEAYVMANA 529* ILKETEFKKLKVLGSGAFGT
220* DNKDILDEAYVMANG 530* ILKETELKKIFVLGPGAFGT
221 * DNKDILDEAYVMANV 531 * ILKETELKKIFVLGSGAFGT
222* DNKDILDEAYVMASA 532* ILKETELKKIKVLGPGAFGT
223* DNKDILDEAYVMASG 533* ILKETELKKIKVLGSGAFGT
224* DNKDILDEAYVMASV 534* ILKETELKKLFVLGPGAFGT
225* DNKDILDEAYVMTCA 535* ILKETELKKLFVLGSGAFGT
226* DNKDILDEAYVMTCG 536* ILKETELKKLKVLGPGAFGT
227* DNKDILDEAYVMTCV 537* ILKETELKKLKVLGSGAFGT
228* DNKDILDEAYVMTIA 538* ILMETEFKKIFVLGPGAFGT
229* DNKDILDEAYVMTIG 539* ILMETEFKKIFVLGSGAFGT
230* DNKDILDEAYVMTIV 540* ILMETEFKKIKVLGPGAFGT
231 * DNKDILDEAYVMTNA 541 * ILMETEFKKIKVLGSGAFGT
232* DNKDILDEAYVMTNG 542* ILMETEFKKLFVLGPGAFGT
233* DNKDILDEAYVMTNV 543* ILMETEFKKLFVLGSGAFGT
234* DNKDILDEAYVMTSA 544* ILMETEFKKLKVLGPGAFGT
235* DNKDILDEAYVMTSG 545* ILMETEFKKLKVLGSGAFGT
236* DNKDILDEAYVMTSV 546* ILMETELKKIFVLGPGAFGT 237* DNKEILDEAYVMACA 547* ILMETELKKIFVLGSGAFGT
238* DNKEILDEAYVMACG 548* ILMETELKKIKVLGPGAFGT
239* DNKEILDEAYVMACV 549* ILMETELKKIKVLGSGAFGT
240* DNKEILDEAYVMAIA 550* ILMETELKKLFVLGPGAFGT
241 * DNKEILDEAYVMAIG 551 * ILMETELKKLFVLGSGAFGT
242* DNKEILDEAYVMAIV 552* ILMETELKKLKVLGPGAFGT
243* DNKEILDEAYVMANA 553* ILMETELKKLKVLGSGAFGT
244* DNKEILDEAYVMANG 554* KGNYVVTDHGSCVRA
245* DNKEILDEAYVMANV 555* KVKIPVAIKAPKA
246* DNKEILDEAYVMASA 556 KVKIPVAIKELREATSPKA
247* DNKEILDE AY VM AS G 557* KVKIPVAIKSPKA
248* DNKEILDEAYVMASV 558 LLRILKETEFKKI
249* DNKEILDEAYVMTCA 559* LLRILKETESKKI
250* DNKEILDEAYVMTCG 560* MNYLEDRLLVHRD
251 * DNKEILDEAYVMTCV 561 MNYLEDRRLVHRD
RLLQERELLEPLTP S GE APNQ AF
252* DNKEILDEAYVMTIA 562*
LR
RLLQERELLEPLTPSGEAPNQAL
253* DNKEILDEAYVMTIG 563*
LR
RLLQERELLEPLTPSGEAPNQAP
254* DNKEILDEAYVMTIV 564*
LR
RLLQERELVEPLTPSGEAPNQAF
255* DNKEILDEAYVMTNA 565*
LR
RLLQERELVEPLTPSGEAPNQAL
256* DNKEILDEAYVMTNG 566
LR
RLLQERELVEPLTPSGEAPNQAP
257* DNKEILDEAYVMTNV 567*
LR
258* DNKEILDEAYVMTSA 568* TLKETEFKKIFVLGPGAFGT
259* DNKEILDE AY VMT S G 569* TLKETEFKKIFVLGSGAFGT
260* DNKEILDE AY VMT S V 570* TLKETEFKKIKVLGPGAFGT
261 * DSKDILDEAYVMACA 571 * TLKETEFKKIKVLGSGAFGT
262* DSKDILDEAYVMACG 572* TLKETEFKKLFVLGPGAFGT
263* DSKDILDEAYVMACV 573* TLKETEFKKLFVLGSGAFGT
264* DSKDILDEAYVMAIA 574* TLKETEFKKLKVLGPGAFGT
265* DSKDILDEAYVMAIG 575* TLKETEFKKLKVLGSGAFGT
266* DSKDILDEAYVMAIV 576* TLKETELKKIFVLGPGAFGT
267* DSKDILDEAYVMANA 577* TLKETELKKIFVLGSGAFGT
268* DSKDILDEAYVMANG 578* TLKETELKKIKVLGPGAFGT
269* DSKDILDEAYVMANV 579* TLKETELKKIKVLGSGAFGT
270* DSKDILDEAYVMASA 580* TLKETELKKLFVLGPGAFGT
271 * DSKDILDEAYVMASG 581 * TLKETELKKLFVLGSGAFGT
272* DSKDILDEAYVMASV 582* TLKETELKKLKVLGPGAFGT
273* DSKDILDEAYVMTCA 583* TLKETELKKLKVLGSGAFGT
274* DSKDILDEAYVMTCG 584* TLMETEFKKIFVLGPGAFGT
275* DSKDILDEAYVMTCV 585* TLMETEFKKIFVLGSGAFGT
276* DSKDILDEAYVMTIA 586* TLMETEFKKIKVLGPGAFGT
277* DSKDILDEAYVMTIG 587* TLMETEFKKIKVLGSGAFGT
278* DSKDILDEAYVMTIV 588* TLMETEFKKLFVLGPGAFGT
279* DSKDILDEAYVMTNA 589* TLMETEFKKLFVLGSGAFGT
280* DSKDILDEAYVMTNG 590* TLMETEFKKLKVLGPGAFGT 281 * DSKDILDEAYVMTNV 591 * TLMETEFKKLKVLGSGAFGT
282* DSKDILDEAYVMTSA 592* TLMETELKKIFVLGPGAFGT
283* DSKDILDEAYVMTSG 593* TLMETELKKIFVLGSGAFGT
284* DSKDILDEAYVMTSV 594* TLMETELKKIKVLGPGAFGT
285* DSKEILDEAYVMACA 595* TLMETELKKIKVLGSGAFGT
286* DSKEILDEAYVMACG 596* TLMETELKKLFVLGPGAFGT
287* DSKEILDEAYVMACV 597* TLMETELKKLFVLGSGAFGT
288* DSKEILDEAYVMAIA 598* TLMETELKKLKVLGPGAFGT
289* DSKEILDEAYVMAIG 599* TLMETELKKLKVLGSGAFGT
290* DSKEILDEAYVMAIV 600 VKITDFGLAKLLGA
291 * DSKEILDEAYVMANA 601 * VKITDFGRAKLLGA
292* DSKEILDEAYVMANG 602 YLEDR LVHRDLA
293* DSKEILDEAYVMANV 603 KVKIPVAIKELREATSPKA
294* DSKEILDEAYVMASA 604* KVKIPVAIKAPKA
295* DSKEILDEAYVMASG 605* KVKIPVAIKAPTS
296* DSKEILDEAYVMASV 606* KVKIPVAIKDPKA
297* DSKEILDEAYVMTCA 607* KVKIPVAIKELKA
298* DSKEILDEAYVMTCG 608* KVKIPVAIKEPKA
299* DSKEILDEAYVMTCV 609* KVKIPVAIKEQKA
300* DSKEILDEAYVMTIA 610* KVKIPVAIKESKA
301 * DSKEILDEAYVMTIG 611 * KVKIPVAIKEVPK
302* DSKEILDEAYVMTIV 612* KVKIPVAIKIPKA
303* DSKEILDEAYVMTNA 613* KVKIPVAIKSPKA
304* DSKEILDEAYVMTNG 614* KVKIPVAIKTPKA
305* DSKEILDEAYVMTNV 615* KIPVAIKEASPKA
306* DSKEILDEAYVMTSA 616* KIPVAIKEFSPKA
307* DSKEILDEAYVMTSG 617* KIPVAIKENSPKA
308* DSKEILDEAYVMTSV 618* KIPVAIKVASPKA
309 HYQDPHSTAVGNPEY 619* KIPVAIKVPSPKA
310* KVKIPVAIAPSPKA
Table 4: Seq.Id.No. 1-619 of human EGFR peptides, * indicates mutated EGFR
Experiments
Peptide Arrays
Peptide arrays were created by PepStar™ (JPT Peptide Technologies GmbH, Berlin, Germany) peptide microarray platform to generate customized peptide microarrays on glass slides for biomarker discovery, immunomonitoring and detection and validation of protein interactions. Peptides are immobilized on glass slides via a flexible linker. Chemoselective coupling generates microarrays of directed and covalently attached peptides.
3661 specified native peptides with 500 scrambled control sequences covering the sequences of EGF-receptor, Arachidonate 15 -lipoxygenase B (LX15B) and p53 and variants thereof were synthesized and arrays printed. A serum dilution 1 :200 was used for the detection of EGFR binding in NSCLC patient samples. Incubation of microarrays was performed in an automated Hybridization Station HS4800 (Tecan) at 30°C. After washing, bound immunoglobine G (IgG) was detected with Cy5-labeled-anti-human secondary antibody (JIR, 0.1 μ /ηι1 end-conc. in assay). Fluorescence was read using a Microarray Scanner GenePix with Autoloader 4200AL (Molecular Devices). Signal intensity is displayed as relative fluorescence units. The following tables detail the wash and incubation conditions:
Figure imgf000047_0001
Table 5 : experimental conditions
Figure imgf000047_0002
Table 6: experimental conditions
Samples
Samples were selected from patients belonging to the TASK study. TASK was a 200- patient randomized, open label, Phase II study of Tarceva® in combination with Avastin® (bevazizumab) compared to standard chemotherapy regimens (gemcitabine plus cisplatin or paclitaxel plus carboplatin) plus Avastin® in first-line NSCLC patients. Further enrollment on this study was halt after data from a pre-planned interim analysis of the first 120 patients. Occurrence of rash was recorded as adverse event. Biopsies from all patients were tested for the occurrence of EGFR mutations and the mutation status has been recorded.
For the peptide array study, a total of 49 patients from both arms (24 Avastin® and Tarceva® (A+T), 25 Avastin® and chemotherapy (A+C)) have been used. In the patients chosen for the A+T arm, rash occurred in 16 patients. In comparison, only 3 patients in the A+C arm developed rash. This corresponds to the expected frequency of rash, as rash is induced by erlotinib, but only to a very limited extend by chemotherapy. Clinical data accessible included outcome data, e.g. response overall survival and progression free survival as well as the rash grade and the mutation status of EGFR as measured from a pre-treatment biopsy.
Statistical Analysis Global test
The following approach to model the data was applied:
• Descriptive statistics (using appropriate single variable) tests to identify covariates as candidates for a linear regression model describing the performance parameter (PFS or OS). · Identification of the best model for efficacy parameters (survival analysis)
• Addition of antibody titer and its interaction with treatment to the model and comparison of the performance with the new variables
With a general model selected, tests on antibody titers within groups of covariates of interest were conducted: · Proportional hazard model by EGFR mutation (EGFRM), Thoracic Radiotherapy (TRT), rash of efficacy parameters vs. antibody abundance (two sample groups - low/high abundance - divided by median)
• U- tests within wild type (WT+) in A+T arm of antibody titer vs. responders/non- responders · l tests by EGFRM and TRT of responses (weeks 6, 12) vs. antibody abundance
Finally, various very similar peptide sequences that yield highly correlated antibody titers were used. For most of the reported peptide sequences, consensus sequence from a listing of all peptides with very high sequence similarity (Smith- Waterman alignment similarity score >50, using a PAM30 substitution matrix and a gap penalty of 1) was selected and antibody titers were correlated to the target titer (Spearman Rank correlation >0.75).
1 Koizumi, K., S. Hojo, et al. (2007). "Chemokine receptors in cancer metastasis and cancer cell- derived chemokines in host immune response." Cancer Science 98(11): 1652-1658
2 Li Yuan et al, Chinese Journal of Lung Cancer, 13(7), 2010, 727-730
3 Li Yuan et al, Chinese Journal of Lung Cancer, 12(10), 2009, 1999-6187 4 C J Chapman, A Murray, J E McElvccn, U Sahin, U Luxemburger, O Tiireci, R Wicwrodt, A C
Barnes, J F Robertson, "Autoantibodies in lung cancer: possibilities for early detection and subsequent cure", Thorax 2008;63(3):228-233
5 WO2011073905
6 Albert, M. L. and R. B. Darnell (2004). "Paraneoplastic neurological degenerations: Keys to tumor immunity." Nat. Rev. Cancer 4(1): 36-44
7 Paz-Ares, L., D. Soulieres, et al. (2010). "Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis." J Cell Mol Med 14(1-2): 51-69
8 Reck, M., A. Hermes, et al. (2011). "Tissue sampling in lung cancer: A review in light of the MERIT experience." Lung Cancer 74(1): 1-6
9 Rosell et al, N Engl J Med 2009; 361 :958-967
10 Mok et al, N Engl J Med 2009; 361 :947-957
11 Heigener, D. and M. Reck (2011). "Mutations in the epidermal growth factor receptor gene in non-small cell lung cancer: Impact on treatment beyond gefitinib and erlotinib." Advances in Therapy 28(2): 126-133
12 Reck, M., A. Hermes, et al. (2011). "Tissue sampling in lung cancer: A review in light of the MERIT experience." Lung Cancer 74(1): 1-6

Claims

Claims
1. A method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
2. The method according to claim 1, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
3. The method according to any of claims 1-2, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id.
No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq.
Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39,
Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No.
45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq.
Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62,
Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No.
69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id.
No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86,
Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No.
92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id.
No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104,
Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115,
Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id.
No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126,
Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id.
No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id.
No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148,
Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 601, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
4. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
5. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No.
17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id.
No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq.
Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34,
Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id.
No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq.
Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57,
Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No.
63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq.
Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81,
Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No.
87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id.
No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No.
105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110,
Seq. Id. No. I l l, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id.
No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121,
Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132,
Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id.
No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143,
Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id.
No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id.
No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165,
Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id.
No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
6. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
7. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
8. The method according to any of claims 1-7, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
9. Erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method of any of claims 1 to 8 comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
10. Use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method of any of claims 1 to 8.
11. A kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
12. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
13. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
14. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58,
Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No.
65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id.
No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82,
Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No.
88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id.
No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq.
Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. I l l,
Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id.
No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122,
Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id.
No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id.
No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144,
Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id.
No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155,
Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166,
Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id.
No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177,
Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id.
No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id.
No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199,
Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id.
No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210,
Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221,
Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id.
No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232,
Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id.
No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id.
No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254,
Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id.
No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265,
Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
15. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id.
No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540,
Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id.
No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551,
Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565,
Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id.
No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577,
Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id.
No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id.
No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
16. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
17. A method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
18. The method according to claim 16, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 519, Seq. Id. No. 520, Seq.
Id. No. 521 and Seq. Id. No. 561.
19. The method according to any of claims 17-18, wherein the autoantibody recognizes an
EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No.
3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9,
Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id.
No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq.
Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32,
Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No.
38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq.
Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55,
Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No.
61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 64, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id.
No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78,
Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No.
84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id.
No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq.
Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 102, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id.
No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. I l l, Seq. Id. No. 112,
Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id.
No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123,
Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134,
Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id.
No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145,
Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id.
No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id.
No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167,
Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id.
No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178,
Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189,
Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id.
No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200,
Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id.
No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 309, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 370, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 373, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 525, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 561, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 566, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 600, Seq. Id. No. 601, Seq. Id. No. 602, Seq. Id. No. 603, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618, and Seq. Id. No. 619.
20. The method according to any of claims 19, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
21. The method according to any of claims 17-20, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
22. Erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method of any of claims 17 to 21 comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
23. Use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method of any of claims 17 to 21.
24. A kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non- small cell lung cancer.
25. A kit according to claim 24, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id. No.9, Seq. Id. No.10, Seq. Id. No. l l, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
26. A kit according to claim 25, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, and Seq. Id. No.561.
27. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
28. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
29. The method according to claim 27 or 28, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No.
555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
30. The method according to any of claims 28-29, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No.
22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id.
No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq.
Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39,
Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id.
No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq.
Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62,
Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No.
69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq.
Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86,
Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No.
92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id.
No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id.
No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115,
Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id.
No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126,
Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 601, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
31. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No.
2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
32. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq.
Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34,
Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No.
40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id.
No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57,
Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No.
63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id.
No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq.
Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No.
87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id.
No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq.
Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No.
105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. I l l, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id.
No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121,
Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id.
No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132,
Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143,
Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id.
No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154,
Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
33. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
34. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id.
No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
35. The method according to any of claims 27-34 wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
36. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
37. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, b) comparing the level of said autoantibody to a reference level, and c) recommending a treatment when the level of said autoantibody is above the reference level.
38. The method according to claim 36 or 37, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No.3, Seq. Id. No.8, Seq. Id.
No.9, Seq. Id. No.10, Seq. Id. No.11, Seq. Id. No.12, Seq. Id. No.13, Seq. Id. No.14, Seq. Id. No.64, Seq. Id. No.102, Seq. Id. No.309, Seq. Id. No.370, Seq. Id. No.373, Seq. Id. No.519, Seq. Id. No.520, Seq. Id. No.521, Seq. Id. No.525, Seq. Id. No.556, Seq. Id. No.558, Seq. Id. No.561, Seq. Id. No.566, Seq. Id. No.600, Seq. Id. No.602 and Seq. Id. No.603.
39. The method according to any of claims 36-38, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
40. The method according to any of claims 28-35, 37-39, wherein the treatment is erlotinib.
41. The invention as herein described.
PCT/EP2013/061430 2012-06-07 2013-06-04 Autoimmune antibodies WO2013182537A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CA2870015A CA2870015A1 (en) 2012-06-07 2013-06-04 Autoimmune antibodies
JP2015515492A JP2015527564A (en) 2012-06-07 2013-06-04 Autoimmune antibody
EP13726532.8A EP2858669A1 (en) 2012-06-07 2013-06-04 Autoimmune antibodies
CN201380027063.XA CN104334190A (en) 2012-06-07 2013-06-04 Autoimmune antibodies
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